Apparently back in the 30s, the Soviet Union was doing research on influenza, some of which used human volunteers.1 Well, better flu research than smallpox or something, and it seems to have worked out alright.
Here, they tried infecting 72 volunteers with virus taken from infected mice, by aerosolizing it and letting them inhale it. It seemed to work in some of the volunteers, though their illness was mild; the authors speculate that the virus might have been attenuated by passage through animals.
The most interesting result was the antibody levels in the volunteers before and after inoculation. They measured antibodies by drawing blood, mixing it with live virus, and injecting it into mice. If the mice survived, the virus had been neutralized by the antibodies.
What they saw was that volunteers who did get sick had pretty low antibodies to begin with, almost none in some cases; afterward their levels were 25-100 times higher. In those that didn't get sick, the levels had started out high and risen only a little (to about the same level as the others). So antibody levels correlated well with immunity to influenza.
The authors thought this infection with somewhat-attenuated virus method might be a good strategy for immunization. The editor of this study's journal disagreed with that statement, as did later researchers:
References:
1. Smorodintseff, A. A., Tushinsky, M. D., Drobyshevskaya, A. I., Korovin, A. A. & Osetroff, A. I. Investigation on Volunteers Infected with the Influenza Virus. The American Journal of the Medical Sciences 194, 159–170 (1937).
2. Rickard, E. R., Horsfall, F. L., Jr., Hirst, G. K. & Lennette, E. H. The Correlation between Neutralizing Antibodies in Serum against Influenza Viruses and Susceptibility to Influenza in Man. Public Health Reports (1896-1970) 56, 1819–1834 (1941).
3. Horsfall, Jr., F. L. Recent Studies in Influenza. Am J Public Health Nations Health 31, 1275–1280 (1941).
4. Kilbourne, E. D. in History of Vaccine Development (ed. Plotkin, S. A.) 137–144 (Springer New York, 2011).
Here, they tried infecting 72 volunteers with virus taken from infected mice, by aerosolizing it and letting them inhale it. It seemed to work in some of the volunteers, though their illness was mild; the authors speculate that the virus might have been attenuated by passage through animals.
The most interesting result was the antibody levels in the volunteers before and after inoculation. They measured antibodies by drawing blood, mixing it with live virus, and injecting it into mice. If the mice survived, the virus had been neutralized by the antibodies.
What they saw was that volunteers who did get sick had pretty low antibodies to begin with, almost none in some cases; afterward their levels were 25-100 times higher. In those that didn't get sick, the levels had started out high and risen only a little (to about the same level as the others). So antibody levels correlated well with immunity to influenza.
The authors thought this infection with somewhat-attenuated virus method might be a good strategy for immunization. The editor of this study's journal disagreed with that statement, as did later researchers:
"A paper published from the Soviet Union by Smorodintsev[sic] et al. in 1937 - frequently cited as the first paper on live virus vaccine - described the administration of a mouse-lethal strain of the...virus by protracted inhalation of atomized virus. Typical febrile influenza developed in 20% of volunteers, hardly an acceptable vaccine by present standards, and certainly not attenuated, as claimed by the authors. Remarkably, they claimed, as well, that the virus appeared not to multiply in men, but the study was a landmark in establishing unequivocally the role of the virus in the development of the disease and in demonstrating antibody response to the virus during convalescence."4Others questioned whether this study could really be compared to natural infections:
"These results suggested that the level of neutralizing antibodies was of significance in determining susceptibility or immunity to influenza A in man. But the conditions under which the experimental disease was produced and the relatively large quantities of virus suspensions used seem so different from conditions encountered in the natural epidemic disease as to make comparisons between these two conditions hazardous."2
"Whether experimentally induced influenza A in human beings is entirely analogous to the naturally occurring epidemic disease may be open to some question."3Seems like a reasonable question, but at least it's easier to control this kind of study for unwanted variables.
References:
1. Smorodintseff, A. A., Tushinsky, M. D., Drobyshevskaya, A. I., Korovin, A. A. & Osetroff, A. I. Investigation on Volunteers Infected with the Influenza Virus. The American Journal of the Medical Sciences 194, 159–170 (1937).
2. Rickard, E. R., Horsfall, F. L., Jr., Hirst, G. K. & Lennette, E. H. The Correlation between Neutralizing Antibodies in Serum against Influenza Viruses and Susceptibility to Influenza in Man. Public Health Reports (1896-1970) 56, 1819–1834 (1941).
3. Horsfall, Jr., F. L. Recent Studies in Influenza. Am J Public Health Nations Health 31, 1275–1280 (1941).
4. Kilbourne, E. D. in History of Vaccine Development (ed. Plotkin, S. A.) 137–144 (Springer New York, 2011).
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